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Eur J Cancer. 2008 Jan;44(1):84-91. Epub 2007 Nov 26.

The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in patients with advanced breast cancer: results of a phase I study with pharmacokinetics.

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  • 1Medical Oncology Clinic, Institut Jules Bordet, Brussels, Belgium. ahmad.awada@bordet.be

Abstract

PURPOSE:

To investigate the safety and pharmacokinetics (PK) of combined treatment with letrozole and the oral mTOR inhibitor RAD001 in patients with metastatic breast cancer stable or progressing after > or = 4 months on letrozole alone.

METHODS:

Eighteen patients received letrozole (2.5 mg/day) and RAD001 at 5 mg/day (cohort 1) or 10 mg/day (cohort 2). In the absence of DLT in cohort 1, cohort 2 was expanded to 12 patients to obtain additional safety and PK data.

RESULTS:

Most common adverse events were stomatitis (50.0% of patients), fatigue (44.4%), anorexia and/or decreased appetite (44.4%), diarrhoea (38.9%), headache (33.3%) and rash (33.3%). There was 1 DLT, a grade 3 thrombocytopaenia in cohort 2. No clinically relevant PK interaction was detected. Seven patients received the combination therapy for >6 months. One patient had a complete response, and one had a 28% reduction in liver metastases, both in cohort 2.

CONCLUSION:

Daily therapy with RAD001 plus letrozole is promising: the results suggest anti-tumour activity with no PK interactions. The overall safety profile of the combination is consistent with that expected for RAD001 monotherapy. A daily dose of RAD001 10mg is recommended for further trials.

PMID:
18039566
[PubMed - indexed for MEDLINE]
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